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Cardiac SarcoidosisPhase 3CHASM-CS-RCTNCT03593759

Cardiac Sarcoidosis Randomized Trial

A Phase 3 study testing Prednisone or Prednisolone and Methotrexate in people with Cardiac Sarcoidosis and Sarcoidosis, run by Ottawa Heart Institute Research Corporation at 31 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Prospective randomized controlled trial comparing low dose Prednisone(or Prednisolone)/Methotrexate combination to standard dose Prednisone(or Prednisolone) in patients diagnosed with acute active clinically manifest cardiac sarcoidosis and not yet treated. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cardiac Sarcoidosis, Sarcoidosis
What is being tested?
Prednisone or Prednisolone and Methotrexate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
31 sitesin 5 countries
Study dates
15 Jan 2019to Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cardiac sarcoidosis presenting with one or more of the following clinical findings:
  • advanced conduction system disease (defined as Mobitz II AV block or third degree AV block)
  • significant sinus node dysfunction (defined as average HR less than 40bpm when awake and/or sustained atrial arrhythmias)
  • non- sustained or sustained ventricular arrhythmia
  • left ventricular dysfunction (LVEF < 50%)
  • right ventricular dysfunction (RVEF < 40%)
Show all 13Show fewer
  • AND
  • No alternative explanation for clinical features
  • AND
  • Nuclear Imaging within six-months of enrollment consisting of FDG-PET scan with FDG uptake suggestive of active CS and myocardial perfusion imaging
  • AND ONE OR BOTH OF FOLLOWING
  • Positive biopsy for Sarcoid (either EMB or extra-cardiac)
  • CT Chest showing features consistent with pulmonary sarcoidosis and/or mediastinal and/or hilar lymphadenopathy

Who cannot join

  • Current or recent (within two months) non-topical treatment for sarcoidosis
  • Current Oral/IV treatment of duration greater than 5 days
  • Currently taking Methotrexate or Prednisone for another health condition
  • Intolerance or contra-indication to Methotrexate or Prednisone
  • Patient does not meet all of the above listed inclusion criteria
  • Patient is unable or unwilling to provide informed consent
Show all 12Show fewer
  • Patient is included in another randomized clinical trial
  • Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
  • Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
  • Breastfeeding
  • Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
  • Patients for whom the investigator believes that the trial is not in the interest of the patient

Trial locations and contacts

31 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

David H Birnie, MD contact

613-696-7269

dbirnie@ottawaheart.ca

Janine Ryan, BAH, CCRP contact

613-696-7000 ext. 17077

jryan@ottawaheart.ca

31 sites in 5 countries

Canada11 sites, 11 recruiting

  • Libin Cardiovascular Institute of Alberta

    Calgary, Alberta, T2N 2T9

    Russell Quinn, MD, 403-220-5500, frquinn@ucalgary.ca

    Russell Quinn, MD

    Recruiting

  • QE II Health Sciences Centre

    Halifax, Nova Scotia, B3H 3A7

    Doug Hayami, MD, doug.hayami@nshealth.ca

    Doug Hayami, MD

    Recruiting

  • St. Joseph's Healthcare Centre

    Hamilton, Ontario, L8N 4A6

    Nathan Hambly, MD, 905-521-6183, nathan.hambly@medportal.ca

    Nathan Hambly, MD

    Recruiting

  • London Health Sciences Centre

    London, Ontario, N6A 4A5

    Nikolaos Tzemos, MD, 519-663-3038, Niko.Tzemos@lhsc.on.ca

    Nikolaos Tzemos, MD

    Recruiting

  • Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

    Genevieve Giraldeau, MD, 514-376-3330 ext. 3858, genevieve.giraldeau@umontreal.ca

    Genevieve Giraldeau, MD

    Recruiting

  • CIUSSS-Hopital du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

    Leila Laroussi, MD, 514-338-2050, liloularoussi@gmail.com

    Leila Laroussi, MD

    Recruiting

  • University of Ottawa Heart Institute

    Ottawa, Ontario, K1Y 4W7

    David H Birnie, MD, 613-696-7269, dbirnie@ottawaheart.ca

    David Birnie, MD

    Recruiting

  • Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval

    Québec, Quebec, G1V 4G5

    Mario Senechal, MD, Mario.Senechal@criucpq.ulaval.ca

    Mario Senechal, MD

    Recruiting

  • CIUSSS de l'Estrie - CHUS - Hôpital Fleurimont

    Sherbrooke, Quebec, J1H 5N4

    Felix Ayala-Paredes, MD, 819-346-1110 ext. 16317, felix.ayala-paredes@USherbrooke.ca

    Felix Ayala-Paredes, MD

    Recruiting

  • Eastern Health Health Sciences Centre

    St. John's, Newfoundland and Labrador, A1B 3V6

    Stephen Duffett, MD, 709-777-6917, sduffett@mun.ca

    Stephen Duffett, MD

    Recruiting

  • St. Paul's Hospital

    Vancouver, British Columbia, V5Z 1M9

    Mustafa Toma, MD, 604 806 9986, MToma@providencehealth.bc.ca

    Mustafa Toma, MD

    Recruiting

Other trials in Canada

United States9 sites, 9 recruiting

  • University of Michigan-Michigan Medicine Cardiovascular Center

    Ann Arbor, Michigan, 48109-5853

    Todd Koelling, MD, 734-936-5265, tkoellin@med.umich.edu

    Todd Koelling, MD

    Recruiting

  • Tufts Medical Center

    Boston, Massachusetts, 02111

    Mili Mehta, MD

    Amanda Vest, MD

    Recruiting

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

    Steven Kalbfleisch, MD, steven.kalbfleisch@osumc.edu

    Steven Kalbfleisch, MD

    Recruiting

  • University of Minnesota

    Minneota, Minnesota, 55455

    C Shenoy, MD

    C Shenoy, MD

    Not yet recruiting

  • Yale-New Haven Hospital

    New Haven, Connecticut, 06520

    Edward Miller, MD, 203-737-8871, edward.miller@yale.edu

    Edward Miller, MD

    Recruiting

  • Montefiore Medical Center

    New York, New York, 10467

    Yogita Rochlani, MD, yrochlani@montefiore.org

    Yogita Rochlani, MD

    Recruiting

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

    Indu Poornima, MD, indu.poornima@ahn.org

    Indu Poornima, MD

    Recruiting

  • Virginia Commonwealth University

    Richmond, Virginia, 23298-0053

    Jordana Kron, MD, 804-828-7565, jordana.kron@vcuhealth.org

    Jordana Kron, MD

    Recruiting

  • University of Utah

    Salt Lake City, Utah, 84112

    Line Kemeyou, MD, line.kemeyou@hsc.utah.edu

    Line Kemeyou, MD

    Recruiting

Other trials in United States

Japan8 sites, 8 recruiting

  • Chiba University

    Chiba

    Y Koboyashi, MD

    Y Koboyashi

    Recruiting

  • University of Fukui

    Fukui

    H Tada, MD

    H Tada, MD

    Not yet recruiting

  • St. Marrianna University

    Kawasaki

    Y. Akashi, MD

    Y Akashi, MD

    Not yet recruiting

  • Nagoya City University

    Nagoya

    K Nakasuka, MD, kosuke.nakasuka@gmail.com

    K Nakasuka, MD

    Recruiting

  • National Cerebral and Cardiovascular Center (NCVC)

    Osaka

    Kengo Kusano, MD, kusanokengo@gmail.com

    Kengo Kusano, MD

    Recruiting

  • Hokkaido University

    Sapporo, Kita 8, Nishi 5, Kita-Ku, 060-0808

    Toshiyuki Nagai, MD, nagai@med.hokudai.ac.jp

    Toshiyuki Nagai, MD

    Recruiting

  • Sapporo Medical University

    Sapporo

    Toshiyuki Yano, MD, tyano@sapmed.ac.jp

    Toshiyuki Yano, MD

    Recruiting

  • Nippon Medical School

    Tokyo

    Kenji Yodogawa, MD, yodo@nms.ac.jp

    Kenji Yodagawa, MD

    Recruiting

Other trials in Japan

United Kingdom2 sites, 2 recruiting

  • King's College Hospital NHS Foundation Trust

    London, SE5 9RS

    Francis D Murgatroyd, MD, +44 (0)20 32993217, francis.murgatroyd@nhs.net

    Francis D Murgatroyd, MD

    Not yet recruiting

  • Imperial College Healthcare Trust-NHS-Hammersmith Hospital

    London, W12 0HS

    Amanda Varnava, MD, amanda.varnava@nhs.net

    Amanda Varnava, MD

    Not yet recruiting

Other trials in United Kingdom

New Zealand1 site, 1 recruiting

  • Auckland City Hospital

    Auckland, Grafton, 1023

    Nicola Edwards Dr., MD

    Recruiting

Other trials in New Zealand

About this study

Official title: Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial

Prospective randomized controlled trial comparing low dose Prednisone(or Prednisolone)/Methotrexate combination to standard dose Prednisone(or Prednisolone) in patients diagnosed with acute active clinically manifest cardiac sarcoidosis and not yet treated.

The Investigators hypothesize that low dose Prednisone(or Prednisolone)/Methotrexate combination will be as effective as standard dose Prednisone(or Prednisolone), and result in significantly better quality of life and less toxicity than standard dose Prednisone(or Prednisolone).

Read the detailed description

Subjects meeting the study inclusion/exclusion criteria will be randomized equally to receive either:

Everywhere but Japan:

  1. Prednisone 0.5 mg kg/day for 6-months (MAX dose 30 mg per day) or
  2. Methotrexate 15-20 mg po, sc, or IM once a week for 6-months + Folic Acid OD (exact dose and directions at physician) for 6 months + Prednisone 20 mg day for 1 month, then 10 mg OD for 1 month, then 5 mg OD for one month then STOP

In Japan:

  1. Prednisone or prednisolone 0.5 mg/kg po (max 30mg) for one month then reduce by 5 mg per month for five months or
  2. Methotrexate 5-20mg po, sc or IM once week for 6-months +Folic Acid 2-5 mg OD for 6-months+Prednisone or prednisolone 20mg OD for 1 month then 10mg OD for 1 month then 5 mg OD one month

Methotrexate will be initiated at a dose of 15 mg once a week and increased to 20 mg once a week after 4 weeks if tolerated. In case of Methotrexate-induced side-effects general guidelines will be provided, however specific management will be left to the treating physicians. Folic acid will be taken to help reduce methotrexate side-effects.

Prior to randomization and study treatment all subjects will have the following baseline tests done: baseline safety blood work; FDG-PET scan with myocardial perfusion imaging; ECG; echo; and an optional bone mineral density scan. Cardiac MRI (CMR) is optional but strongly encouraged. Blood will be obtained for biomarker core-lab analysis. Biomarkers to be assayed will include highly sensitive Troponin I. Samples will be stored for future novel biomarker discovery. Quality of LIfe (QOL) questionnaires (KSQ, SAT and SF-36) will be completed prior to treatment start.

After therapy initiation subjects will be seen at 4 weeks, 8 weeks (methotrexate arm only), and 12 weeks, with a final visit at 6 months. Safety bloodwork and assessment for medication side effects, using a medication side-effect questionnaire, will be completed at all visits. At 12 weeks QOL questionnaires will be completed. The primary endpoint will be assessed at 6-months, when FDG-PET with myocardial perfusion imaging, ECG, echo, optional bone mineral density scan, QOL questionnaires, blood for biomarkers and device interrogation will be done. CMR may be repeated. Skin, muscle strength testing and neuropsychiatric assessment will be completed at 6 months as part of the composite glucocorticoid toxicity index.

After the 6 month visit. further management will be at the treating physician's discretion. Details of the physicians planned treatment following the 6-month PET scan will be collected.

Standardized protocols for all aspects of FDG-PET scans (i.e. patient preparation, image acquisition, image processing, transfer to the core lab and analysis at core lab) will be followed.

Being tested
Prednisone or Prednisolone, Methotrexate
Keywords
Cardiac Sarcoidosis, Prednisone (or Prednisolone), Methotrexate
Medical subject headings
Sarcoidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Prednisone or PrednisoloneDrug

    Oral prednisone/prednisolone tablet

  • MethotrexateDrug

    Oral, subcutaneous, or intramuscular methotrexate

Study groups in NCT03593759
Study groupRoleWhat they receive
Prednisone (or Prednisolone)Active comparator[Dose everywhere except Japan] Prednisone 0.5 mg kg/day for 6 months (max dose 30 mg) [Dose in Japan] Prednisone or prednisolone 0.5 mg/kg po (max 30mg) for one month then reduce by 5 mg per month for five months
Receives: Drug: Prednisone or Prednisolone
MethotrexateExperimental[Dose everywhere except Japan] Methotrexate 15-20 mg orally, sc, or IM once a week for 6 months + Prednisone 20 mg po daily for one month then 10 mg po daily for one month then 5 mg po daily for one month and then stop. Also Folic Acid OD (exact dose and directions at physicians discretion) for 6 months. [Dose in Japan] Methotrexate 5-20mg mg orally, sc, or IM once a week for 6 months+ Prednisone or Prednisolone 20mg OD for 1 month then 10mg OD for 1 month then 5 mg OD one month. Also Folic Acid 2 mg po daily for 6 months.
Receives: Drug: Prednisone or Prednisolone; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Summed perfusion rest score (SPRS) on FDG-PET scan

    Measure of myocardial scarring and fibrosis (blinded core lab analysis)

    Measured: 6 months

Secondary outcomes (19)

  1. Mortality

    All cause deaths

    Measured: 6 months

  2. Cardiovascular hospitalizations

    Cardiovascular related only

    Measured: 6 months

  3. Medication related adverse events

    Using clinical assessment, medication side-effect and adverse event reporting

    Measured: 6 months

  4. Modified Cleveland Clinic Glucocorticoid Toxicity Score

    Summed score of new/worsening diabetes;new/worsening HTN; osteoporosis; change in height and weight (combined and reported as BMI in kg/m2)

    Measured: 6 months

  5. Glucocorticoid Toxicity Index

    Composite scoring (improvement; no significant change; worsening) compared to baseline

    Measured: 6 months

  6. Patient reported symptoms related to medication

    Using medication side-effect questionnaire ( symptom present, yes or no; frequency; intensity)

    Measured: 6 months

  7. Medication compliance

    % of days where treatment was taken as prescribed

    Measured: 6 months

  8. Generic Quality of Life (SF 36)

    Measuring general QOL using SF-36 questionnaire

    Measured: 6 months

  9. Disease Specific Quality of Life (KSQ and SAT)

    Using Kings Sarcoidosis questionnaire and Sarcoidosis Assessment Tool

    Measured: 6 months

  10. BMI

    Weight and height combined to report BMI in kg/m2, absolute and delta compared to baseline

    Measured: 6 months

  11. Blood pressure

    Systolic and diastolic, absolute and delta compared to baseline

    Measured: 6 months

  12. HbA1C

    Absolute and delta compared to baseline

    Measured: 6 months

  13. T-score on bone density scan

    Absolute and delta compared to baseline

    Measured: 6 months

  14. FDG-PET and myocardial perfusion

    SPRS in mismatched segments; SUVmax, SUVmean and COI; LVEF, RVEF; whole body disease activity

    Measured: 6 month scan

  15. Ventricular arrhythmia burden

    Episodes of sustained ventricular arrhythmia or episodes requiring appropriate ICD therapy (shock or anti-tachycardia pacing)

    Measured: 6 months

  16. Complete heart block

    Percentage of patients who are in CHB

    Measured: 6 months

  17. LVEF and RVEF assessed on echocardiogram

    Ejection fraction, absolute and delta compared to baseline

    Measured: 6 months

  18. Highly sensitive Troponin I levels and BNP levels

    Absolute and delta compared to baseline

    Measured: 6 months

  19. CMR Endpoints

    Volume of delayed enhancement

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2018
  2. Study start15 Jan 2019
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, open-label, non-inferiority, randomized controlled with blinded end-point analysis.
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03593759
Sponsor's protocol ID
UOttawaHI
Acronym
CHASM-CS-RCT
Status last verified
Apr 2026
First submitted
27 Jun 2018
Last updated
10 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Birnie D, Beanlands RSB, Nery P, Aaron SD, Culver DA, DeKemp RA, Gula L, Ha A, Healey JS, Inoue Y, Judson MA, Juneau D, Kusano K, Quinn R, Rivard L, Toma M, Varnava A, Wells G, Wickremasinghe M, Kron J. Cardiac Sarcoidosis multi-center randomized controlled trial (CHASM CS- RCT). Am Heart J. 2020 Feb;220:246-252. doi: 10.1016/j.ahj.2019.10.003. Epub 2019 Oct 20.

    PubMed 31911261

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Prednisone or Prednisolone and Methotrexate in people with Cardiac Sarcoidosis and Sarcoidosis, run by Ottawa Heart Institute Research Corporation at 31 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Canada, United States, Japan, United Kingdom, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David H Birnie, MD (613-696-7269, dbirnie@ottawaheart.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Summed perfusion rest score (SPRS) on FDG-PET scan (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03593759, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.

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